Certain well known narcotic analgesics belong to the class of 4,5.alpha.-epoxymorphinan compounds which have the following basic ring system, in which the atoms are numbered as indicated. ##STR2##
The two most familiar compounds of this class are morphine and its 3-methyl ether, codeine, with the structures indicated below. ##STR3##
When the 6-hydroxyl group of each of these compounds is oxidized to an oxo group, the compounds conveniently are referred to as morphinone and codeinone, respectively. When the N-methyl groups of the latter compounds are replaced by other substituent groups they may be referred to as N-substituted normorphinones and norcodeinones, respectively. There are two types of nomenclature commonly used for describing compounds herein. The trivial means, such as morphine or morphinone, are widely accepted and used for the sake of brevity and clarity. The Chemical Abstracts nomenclature is preferred and is used wherever precision is needed.
Morphine and its relatives are used primarily for the relief of pain (i.e., as analgesics). They are narcotic and possess dependence-inducing ability and produce other side effects that make them less than ideal analgesics (emesis, constipation, sweating, respiratory depressions, miosis). A compound with the appropriate profile of analgesic (agonist) and narcotic antagonist actions which is not morphine-like has potential as an analgesic agent for treatment of moderate to severe pain without liability of drug dependence. Furthermore, a compound having only strong narcotic antagonist action may be a desirable agent for treatment of drug dependence.
U.S. patent application Ser. No. 56,549, filed May 26, 1979 discloses 7, 8 and 7-8 substituted 4,5.alpha.-epoxymorphinan-6-one compounds of the formula: ##STR4## where R.sub.1 can be H or methyl, R.sub.2 can be cyclopropylmethyl, cyclobutylmethyl, allyl or tetrahydrofurfuryl, R.sub.3 is H, methyl or ethyl and R.sub.4 is H or methyl. Compounds disclosed in this application have analgesic activity, narcotic antagonist activity or a combination of these activities.